Methods of stimulating cell receptor activity using electromagnetic fields
A method for activating a vascular endothelial growth factor (VEGF) receptor of one or more cells includes positioning an electromagnetic field generator in proximity to a VEGF receptor such that the flux of an electromagnetic field generated by the electromagnetic field generator will extend through the VEGF receptor. The method also includes generating an electromagnetic field, using the electromagnetic field generator, having a rate of fluctuation that activates the VEGF receptor.
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The instant patent application claims priority to U.S. Provisional Patent Application Ser. No. 60/271,030, filed on Feb. 23, 2001.
TECHNICAL FIELD OF THE INVENTIONThis invention relates to the field of stimulating cell receptor activity, and more particularly, to using electromagnetic fields to stimulate cell receptor activity.
BACKGROUND OF THE INVENTIONOsteoporosis is a disease characterized by a decrease in bone mass which leads to a spontaneous bone fracture or fractures occurring due to an impact that under normal conditions would not produce a bone fracture. The goal for treating osteoporosis is to build bone strength to a level sufficient to withstand normal loading conditions without failure. A significant determinant of bone strength is bone mass. Bone mass is determined by the balance between the activity of osteoclast, which destroy bone, and osteoblast, which build bone. During homeostasis, in which bone mass is maintained at a constant level, the activity of the osteoclast and osteoblast are equal. Around the age of thirty, peak bone mass is typically achieved. At this stage the activity of osteoblasts begin to lag behind the activity of osteoclasts. This results in a loss of bone. The health impact of osteoporosis includes loss of the quality of life as osteoporotic bone fractures usually occur in the elderly who have a diminished healing capacity.
One method of treatment is to stimulate osteoblast to form new bone. It is well known in biology that mature, fully differentiated cells do not divide to create new cells. Therefore, to increase the number of bone producing, fully differentiated bone cells it is necessary to first increase the number of pre-osteoblast cells and then induce their maturation into fully differentiated bone cells to reverse the effects of osteoporosis. Furthermore, since new bone cell growth is also needed to heal non-osteoporotic bone fractures and to fuse vertebrae, the stimulation of osteoblasts to form new bone is also useful for treating other fractures and for performing spinal fusion.
SUMMARY OF THE INVENTIONAccording to the present invention, disadvantages and problems associated with previous cell growth stimulation techniques have been substantially reduced or eliminated.
According to one embodiment of the present invention, a method for activating a vascular endothelial growth factor (VEGF) receptor of one or more cells includes positioning an electromagnetic field generator in proximity to a VEGF receptor such that the flux of an electromagnetic field generated by the electromagnetic field generator will extend through the VEGF receptor. The method also includes generating an electromagnetic field, using the electromagnetic field generator, having a rate of fluctuation that activates the VEGF receptor.
In another embodiment of the present invention, a device for activating a VEGF receptor includes a generator operable to generate an electromagnetic field having a rate of fluctuation that activates the VEGF receptor. The device also includes a positioning apparatus operable to position the generator such that the flux of the electromagnetic field will extend through the VEGF receptor.
Particular embodiments of the present invention may provide one or more technical advantages. For example, certain embodiments allow for the reversal of osteoporosis and for stimulating the healing of fractures caused by osteoporosis. Certain embodiments may also be used to increase the rate of healing other bone fractures and to fuse vertebrae. These treatments may be performed without the introduction of growth factors into the body and without the expense associated with producing such growth factors.
Other technical advantages may be readily apparent to those skilled in the art from the figures, description and claims included herein.
To provide a more complete understanding of the present invention and the features and advantages thereof, reference is made to the following description taken in conjunction with the accompanying drawings, in which:
The occurrence of certain events may be communicated to, and detected by, cell receptors 110 through the use of ligands 210. Ligands 210 are typically composed of proteins and travel through intracellular fluid 200 seeking to bind with the cell receptors 110 of cells 105. When the ligand 210 binds with a cell receptor 110, the cell receptor 110 generates a signal 135 which is delivered to the appropriate intracellular machinery 130 inside the cell 105. The signal causes the intracellular machinery 130 to perform certain specific actions. A cell receptor 110 that is bonded to ligand 210 is considered to be in an active state.
One type of ligand 210 that may interact with cell receptor 110 is a growth factor. Examples of such growth factors include, but are not limited to, an insulin-like growth factor-I (IGF-I), an epidermal growth factor (EGF), a vascular endothelial growth factor (VEGF), a basic fibroglast growth factor (bFGF), and transforming growth factor beta (TGFb). The primary function of such growth factors, as well as other ligands, is to activate specific receptors 110 located on the surface of cells 105. For example, cell receptors 110 may include an insulin-like growth factor-I (IGF-I) receptor, an epidermal growth factor (EGF) receptor, a vascular endothelial growth factor (VEGF) receptor, a basic fibroglast growth factor (bFGF) receptor, a transforming growth factor beta (TGFb) receptor, or any other appropriate receptor (some or all of these receptors 110 may be included in cell 105). As can be seen, each growth factor has an associated receptor 110 with which it binds and which it activates to initiate certain biological effects, as described below.
The activation of such receptors and the resultant detection of this change in vibration may cause various actions to occur, depending on the type of receptor 110 that is activated. For example, when a growth factor ligand 210 activates a receptor 110 associated with that growth factor, receptor 110 may generate a signal 135 instructing the intracellular machinery 130 of a pre-osteoblast cell 105 to initiate the division of the cell 105. The activation of another type of receptor 110 by a different growth factor ligand 210 may cause a signal 135 to be generated instructing the intracellular machinery 130 of a cell 105 to differentiate the cell 105 into a particular type of cell, such as a bone cell. Since such cell division and differentiation are required for the development of new bone cells that are necessary to cure osteoporosis and to heal a bone fracture, growth factor ligands 210 and the resulting reactions that are caused when these ligands 210 activate an associated receptor 110 are integral to the natural process of bone cell growth.
Although this receptor activation occurs naturally and regularly in the human body, external sources may be used to change the manner in which an intracellular sub-unit 125 and an extracellular sub-unit 120 vibrate, so as to stimulate bone cell growth. For example, growth factor ligands 210 may be artificially introduced into or stimulated in a person's body to increase the activation of appropriate receptors 110 so as to stimulate cell division and differentiation and help cure osteoporosis and heal bone fractures (or fuse vertebrae). This same cell division and differentiation may also result if alternative techniques are used to activate particular receptors 110. One such technique involves the use of an electromagnetic field (or a magnetic field) to activate receptors 110.
Although example output waveforms have been illustrated in
The peak cell count of 150%, represented by plot 770c, mimics the peak cell count, data point 720d, achieved with the IGF-I ligand solution treatment. Accordingly, IGF-I receptors can be activated, thereby stimulating the growth of MG-63 cells 105, using an electromagnetic field generated by a PEMF generator in a manner similar to the activation of IGF-I receptors using IGF-I ligands.
Accordingly, TGFb receptors can be activated, thereby stimulating the differentiation of MG-63 cells by exposing the receptors to an electromagnetic field fluctuating at a rate between approximately 130 Hz and 140 Hz. Additionally, no statistically significant activity occurred when the electromagnetic field was fluctuated at rates between 375 Hz to 385 Hz (the optimal rates for activating an IGF-I receptor illustrated in
Additional experimentation has shown that various growth factors, such as IGF-I, EGF, VEGF, and bFGF, also cause biological effects (such as cell growth) in normal human bone cells (HBC), normal human cartilage cells (HCC), and normal human vascular endothelial cells (Huvec). Experimentation also has shown that these normal human cell types also respond to PEMF treatment. To further advance the understanding of the biological action caused by PEMF treatment, it is useful to eliminate the effect of particular types of receptors during experimentation so as to determine the involvement of these types of receptors in PEMF treatment. One technique that may be used to eliminate the effect of a particular type of receptor is to use antibodies against particular growth factor receptors.
More specifically, bar 920a represents the percent change in bone cell count twenty-four hours after treatment with an IGF-I growth factor. Bar 920b represents the percent change in cell count twenty-four hours after treatment with an IGF-I growth factor, but where an antibody against the IGF-I receptor (αIR3) was added to the colony before the treatment. As is shown by the lower percent change represented by bar 920b as compared to bar 920a, the addition of the IGF-I antibody decreased cell growth resulting from the introduction of IGF-I growth factor, as compared to the results where no IGF-I receptor antibody was introduced. This is to be expected since the IGF-I receptor antibody impedes the activation of the IGF-I receptor.
Bar 925a represents the percent change in bone cell count twenty-four hours after treatment with a VEGF growth factor. Bar 925b represents the percent change in cell count twenty-four hours after treatment with an VEGF growth factor, but where the antibody to the IGF-I receptor (αIR3) was added to the colony before the treatment. As is shown by the higher percent change represented by bar 925b as compared to bar 925a, the addition of the IGF-I antibody increased bone cell growth resulting from the introduction of VEGF growth factor, as compared to the results where no IGF-I receptor antibody was introduced.
Bar 930a represents the percent change in cell count twenty-four hours after a PEMF treatment. The PEMF treatment used included electromagnetic fields having a waveform the same as or similar to the waveform described in relation to
In summary, the data in the graph shows that normal human bone cells respond to growth factors such as IGF-I and VEGF with an increase in cell growth (as indicated by bars 920a and 925a). Furthermore, treatment with PEMF also increases cell growth (as indicated by bar 930a). When an antibody that blocks the IGF-I receptor is added prior to experimental treatment, the effect of PEMF exposure is not blocked. Furthermore, the fact that the antibody is blocking IGF-I action, but not VEGF action, indicates that the antibody is acting specifically against the IGF-I receptor. Since the antibody did not block the action of the PEMF treatment, this suggests that the PEMF is not acting through the IGF-I receptor.
More specifically, bar 1020a represents the percent change in cell count twenty-four hours after treatment with an IGF-I growth factor. Bar 1020b represents the percent change in cell count twenty-four hours after treatment with an IGF-I growth factor, but where an antibody against the VEGF receptor was added to the colony before the treatment. As is shown, the VEGF receptor antibody has no substantial effect on the percent change in bone cell growth resulting from treatment with an IGF-I growth factor.
Bar 1025a represents the percent change in bone cell count twenty-four hours after treatment with a VEGF growth factor. Bar 1025b represents the percent change in cell count twenty-four hours after treatment with an VEGF growth factor, but where the antibody to the VEGF receptor was added to the colony before the treatment. As is shown by the lower percent change represented by bar 1025b as compared to bar 1025a, the addition of the VEGF antibody decreased bone cell growth resulting from the introduction of VEGF growth factor, as compared to the results where no VEGF receptor antibody was introduced. This is to be expected since the VEGF receptor antibody impedes the activation of the VEGF receptor.
Bar 1030a represents the percent change in bone cell count twenty-four hours after a PEMF treatment. The PEMF treatment used included electromagnetic fields having a waveform the same as or similar to the waveform described in relation to
In summary, the data in the graph shows (as with the graph of
More specifically, bar 1120a represents the percent change in cell count twenty-four hours after treatment with an IGF-I growth factor. Bar 1120b represents the percent change in cell count twenty-four hours after treatment with an IGF-I growth factor, but where an antibody against the IGF-I receptor was added to the colony before the treatment. As is shown by the lower percent change represented by bar 1120b as compared to bar 1120a, the addition of the IGF-I antibody decreased cell growth resulting from the introduction of IGF-I growth factor, as compared to the results where no IGF-I receptor antibody was introduced. This is to be expected since the IGF-I receptor antibody impedes the activation of the IGF-I receptor.
Bar 1125a represents the percent change in cell count twenty-four hours after treatment with a VEGF growth factor. Bar 1125b represents the percent change in cell count twenty-four hours after treatment with an VEGF growth factor, but where the antibody to the IGF-I receptor was added to the colony before the treatment. As is shown by the higher percent change represented by bar 1125b as compared to bar 1125a, the addition of the IGF-I antibody increased cell growth resulting from the introduction of VEGF growth factor, as compared to the results where no IGF-I receptor antibody was introduced.
Bar 1130a represents the percent change in cell count twenty-four hours after a PEMF treatment. The PEMF treatment used included electromagnetic fields having a waveform the same as or similar to the waveform described in relation to
In summary, the data in the graph of
More specifically, bar 1220a represents the percent change in cell count twenty-four hours after treatment with an IGF-I growth factor. Bar 1220b represents the percent change in cell count twenty-four hours after treatment with an IGF-I growth factor, but where an antibody against the VEGF receptor was added to the colony before the treatment. As is shown, the VEGF receptor antibody has a small effect on the percent change in vascular endothelial cell growth resulting from treatment with an IGF-I growth factor.
Bar 1225a represents the percent change in vascular endothelial cell count twenty-four hours after treatment with a VEGF growth factor. Bar 1225b represents the percent change in cell count twenty-four hours after treatment with an VEGF growth factor, but where the antibody to the VEGF receptor was added to the colony before the treatment. As is shown by the lower percent change represented by bar 1225b as compared to bar 1225a, the addition of the VEGF antibody decreased vascular endothelial cell growth resulting from the introduction of VEGF growth factor, as compared to the results where no VEGF receptor antibody was introduced. This is to be expected since the VEGF receptor antibody impedes the activation of the VEGF receptor.
Bar 1230a represents the percent change in vascular endothelial cell count twenty-four hours after a PEMF treatment. The PEMF treatment used included electromagnetic fields having a waveform the same as or similar to the waveform described in relation to
In summary, the data in the graph shows (as with the graph of
Although the present invention has been described with several embodiments, numerous changes, substitutions, variations, alterations, and modifications may be suggested to one skilled in the art, and it is intended that the invention encompass all such changes, substitutions, variations, alterations, and modifications as fall within the spirit and scope of the appended claims.
Claims
1. A method for activating a vascular endothelial growth factor (VEGF) receptor of one or more cells, the method comprising:
- positioning an electromagnetic field generator in proximity to a VEGF receptor such that the flux of an electromagnetic field generated by the electromagnetic field generator will extend through the VEGF receptor; and
- generating an electromagnetic field burst using the electromagnetic field generator having a rate of fluctuation that activates the VEGF receptor,
- wherein the electromagnetic field burst has a burst period of approximately 26 msec, and
- wherein the rate of fluctuation is about 3831 Hertz or about 3861 Hertz.
2. The method of claim 1, wherein the VEGF receptor is part of a human bone cell.
3. The method of claim 1, wherein the VEGF receptor is part of a human vascular endothelial cell.
4. The method of claim 1, wherein VEGF receptors of a plurality of cells are activated by the electromagnetic field.
5. The method of claim 1, wherein the electromagnetic field is generated such that the electromagnetic field causes cell growth to occur that is substantially similar to cell growth that occurs when a VEGF receptor is activated by a VEGF ligand.
6. A method for activating a vascular endothelial growth factor (VEGF) receptor of one or more cells, the method comprising:
- positioning an electromagnetic field generator in proximity to a VEGF receptor such that the flux of an electromagnetic field generated by the electromagnetic field generator will extend through the VEGF receptor; and
- generating an electromagnetic field burst using the electromagnetic field generator having a rate of fluctuation that activates the VEGF receptor,
- wherein the electromagnetic field burst has a burst period of approximately 5.5 msec, and
- wherein the rate of fluctuation is about 3831 Hertz or about 3861 Hertz.
7. The method of claim 6, wherein the VEGF receptor is part of a human bone cell.
8. The method of claim 6, wherein the VEGF receptor is part of a human vascular endothelial cell.
9. The method of claim 6, wherein VEGF receptors of a plurality of cells are activated by the electromagnetic field.
10. The method of claim 6, wherein the electromagnetic field is generated such that the electromagnetic field causes cell growth to occur that is substantially similar to cell growth that occurs when a VEGF receptor is activated by a VEGF ligand.
11. A method for activating a vascular endothelial growth factor (VEGF) receptor of one or more cells, the method comprising:
- positioning an electromagnetic field generator in proximity to a VEGF receptor such that the flux of an electromagnetic field generated by the electromagnetic field generator will extend through the VEGF receptor; and
- generating an electromagnetic field burst using the electromagnetic field generator having a rate of fluctuation that activates the VEGF receptor,
- wherein the electromagnetic field burst has a burst period of approximately 26 msec, and
- wherein the rate of fluctuation is about 62 kHz to 63 kHz.
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6364824 | April 2, 2002 | Fitzsimmons |
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Type: Grant
Filed: Feb 22, 2002
Date of Patent: Aug 8, 2006
Assignee: AMEI Technologies Inc. (Wilimington, DE)
Inventor: Robert J. Fitzsimmons (Colton, CA)
Primary Examiner: Robert S. Landsman
Attorney: Baker & McKenzie LLP
Application Number: 10/080,642
International Classification: A61N 1/08 (20060101); A61N 1/10 (20060101); A61N 1/18 (20060101); A61N 1/20 (20060101); A61N 1/00 (20060101);